Diabetes is comprised primarily of two clinically separate diseases: type 1 and type 2 diabetes. Type 1 diabetes is a cell-mediated autoimmune disease directed against the beta-cells and characterized by autoantibody and T cell reactivity to islet proteins. In contrast, type 2 diabetes is not autoimmune, but rather results from both insulin resistance, and a non-autoimmune insulin secretory defect. However, there is a subgroup of phenotypic type 2 diabetes patients who have autoantibodies and T cell responses to islet cell proteins characteristic of type 1 patients. Several names have been used to describe these patients including latent autoimmune diabetes in adults (LADA), slowly progressive type 1, and type 1.5 diabetes. Differences in immune reactivity to islet proteins have been identified between type 1 and adult type 1.5 diabetes patients. We observed apparent differences in specific islet proteins recognized, the number of islet proteins recognized, and the magnitude of islet cell recognition by T cells from type 1 versus adult type 1.5 diabetes patients. Studies in this grant will focus on identification of islet proteins stimulatory to T cells from both type 1 diabetes patients and adult type 1.5 diabetes patients along with islet proteins that may distinguish these two forms of autoimmune diabetes. Identification of the stimulatory islet proteins will allow for these proteins to be used for diagnostic as well as have clinical applications for monitoring immunomodulatory therapies. [unreadable] [unreadable] [unreadable]